Medical hypotheses最新文献

The practice of sauna has been found to have both acute and long-term cardiovascular benefits, which are generally postulated to be a result of thermoregulatory physiological adaptations. Another element of sauna conditions which has been overlooked is that the extremely high absolute water content of air at sauna temperature, even at low relative humidity, results in significantly decreased partial pressure of oxygen. Using the Arden-Buck equation for water-carrying capacity of air along with the barometric formula, it is shown in this hypothesis that typical sauna conditions have an oxygen partial pressure reduction that may be equivalent to significant elevations above sea level. This effect may also be enhanced by lower air density further reducing available oxygen relative to respiratory volume.

This paper presents the hypothesis that altitude adaptation may be a contributing factor in the cardiovascular benefits of sauna treatments, suggesting that sauna should be considered as an alternative in instances where intermittent hypoxic training is indicated but not available, and that clinical research into sauna treatment is merited for conditions in which intermittent hypoxic training is known to have applications. The hypothesis could be investigated through pulse oximetry of subjects under sauna conditions and by tracking blood markers of altitude adaptation compared to a control group using steam rooms.

Fibromyalgia (FM) is a central chronic pain syndrome with fatigue, sleep disorders, and other symptoms. It has 1–5 % worldwide prevalence, 3:1 female-to-male ratio, and shows correlation with stress. The pathogenic mechanism is unknown, biomarkers are missing, and patient management is extremely difficult due to the lack of resolutive therapies. We developed a pathogenic model of FM based on a thalamocortical loop network that shifts from monostability to bistability for decreasing GABAergic and increasing glutamatergic transmission, leading to the appearance of a high-firing-rate steady state that represents FM altered central pain processing. Here, we propose the hypothesis that the pathogenic GABA/glutamate unbalance could be effectively counteracted by the use of neurosteroid drugs acting as positive allosteric modulators of both synaptic and extrasynaptic GABA_A receptors. Our hypothesis is based on evidence suggesting the involvement of large fluctuations of gonadal neurosteroids (notably brain allopregnanolone withdrawal in perimenstrual/peripartum periods) and of adrenocortical hormones (notably cortisol rise during stress activation) in FM pathogenesis and in the regulation of central GABA/glutamate balance. Therefore, our hypothesis provides a link between FM clinical features (such as female prevalence and correlation with stress) and endocrine influences on neurotransmission, suggesting the use of neurosteroid drugs for the treatment of the disease.

The search for what characteristics define an epitope as either an immunogenic or a non-responsive target for immunotherapy has eluded researchers for years. Several studies demonstrate that certain positions in the peptide sequences, the major histocompatibility complex (MHC) anchor residues, have a preferential composition of amino acids (allelic motifs), being those epitopes more likely to display a better immunogenic response. First of all, not all MHC ligands are immunogenic, considering that unnumbered self-epitopes are continuously presented on the cell surfaces. In this work, we analyzed data to evaluate an additional element, central to our hypothesis that alterations in tumor protein sequences result in a structural change that shifts the electrostatic surface of the peptide-major histocompatibility complex (pMHC) molecules, pivotal for T-Cell receptor (TCR) recognition and the initiation of an immunogenic response. Firstly, previously neoepitope sequences presenting differential immune responses when compared with their wild-type counterparts were recovered. Even though the sequences were very similar, they triggered responses that were considerably different, and currently, there is no well-established explanation for why they conspicuously differ in immunogenic aspects from each other. The pMHCs structures harboring the epitope sequences were modeled and then used to generate images of their electrostatic surfaces, looking for qualitative differences that indicate the distinct responses. We noticed that no significant alteration occurred between immunogenic tumor peptides and their wild-type non-immunogenic counterparts when comparing their electrostatic surface. An additional comparison was made against structures of pMHCs containing immunogenic epitopes recovered from the Crosstope Database (https://crosstope.com.br/). In this sense, it was also possible to verify if immunogenic tumor epitopes were similar to viral immunogenic ones. Surprisingly, both wild-type (WT) sequences and neoepitopes shared an electrostatic surface distribution with pathogen targets, which could indicate their immunogenic predisposition. So we theorized that a “hidden element” may be responsible for the immunogenicity shift in neoepitopes.

As the most commonly used drugs, antibiotics have several adverse effects. When intravenous broad-spectrum antibiotics are administered for infections outside the gut, they are also released into the gut, upsetting the natural balance of flora and potentially causing opportunistic infections there. Pseudomembranous colitis induced by the excessive growth of Clostridioides difficile following antibiotic administration and disruption of the normal gut flora is a main consequence of antibiotic therapy. Unfortunately, effective strategies to mitigate the damage caused by antibiotics to the microbiota remain elusive, with limited information available on the subject. Several studies have examined the effects of enzymatic inactivation of specific antibiotics, but non-enzymatic inactivation of antibiotics has been explored to a lesser extent, resulting in the introduction of only a restricted number of products. We believe that bentonite clay, an underutilized substance that exhibits promising features for counteracting the unfavorable effects of antibiotics has a high potential to circumvent the side effects of antibiotics. It is a cost-effective and safe and has garnered significant attention in the medical history, predominantly for its superior adsorption properties. Given the diverse characteristics of bentonite clay, capacity to protect the natural flora, antibacterial and anti-inflammatory traits, and its contribution to wound healing, it is plausible to assume that bentonite clay exhibits significant potential in mitigating the detrimental consequences of antibiotic on the natural gut microbiota and following pseudomembranous colitis. Further research is necessary to unravel the full extent of its therapeutic effects in combating this condition.

About 40% of women with epilepsy experience catamenial seizures, which can be mentally and physically debilitating. Catamenial epilepsy (CE) refers to the relationship between the timing of a woman’s seizures and the monthly hormonal changes that occur throughout her menstrual cycle. The prevailing hypothesis theorizes that these hormonal changes cause CE seizures. However, researchers have not isolated the catamenial seizure neurological trigger mechanism; as a result, standard anti-seizure medications (ASMs) mostly are ineffective. Recent research substantiates the significant role inflammatory cytokines play in epilepsy, menstrual disorders, and the female reproductive system. This paper poses a new hypothesis that the direct trigger of catamenial seizures is an increase in pro-inflammatory cytokines that occurs at several times during the menstrual cycle. The hypothesis is evaluated using published evidence that the occurrences of catamenial seizures during the menstrual cycle align temporally with the surges in pro-inflammatory cytokines. Consequently, the anti-inflammatory benefits of exercise, endocannabinoid-based drugs and safe, neuroprotective dietary supplements could enable hundreds of thousands of women with catamenial epilepsy to enjoy more productive lives from a much reduced risk of seizures.

Infantile Blount’s disease primarily affects toddlers, leading to tibia vara with or without growth arrest. While the disease’s association with abnormal compressive forces on the proximal tibial physis is widely accepted, its precise aetiopathology remains elusive. This hypothesis suggests that ischaemic chondronecrosis serves as a previously unaddressed cause of Blount’s disease. Notably, it is also the foremost theory to offer a comprehensive explanation for the specificity of involvement of the posteromedial tibial epiphysis, addressing a crucial aspect that was overlooked in prior research. The theory of pressure-induced ischaemic chondronecrosis is supported by a compelling body of radiological and histological evidence. Experimental studies on femoral heads in animals highlight the susceptibility to ischaemic injury in the absence of an ossific nucleus. The proposed mechanism could explain the delayed ossification observed in the proximal medial tibial epiphysis in Blount’s disease. Comparisons with Perthes’ disease reveal striking parallels in radiographic and histological features, pointing toward a shared aetiology of vascular insult. Despite both conditions progressing through similar stages, the distinction lies in Perthes’ being characterised by osteochondral necrosis, while Blount’s results from chondronecrosis. The potential applications of this hypothesis extend to early detection and prevention, emphasising the avoidance of compression on the medial tibial epiphysis. The study suggests a reevaluation of brace therapy and exploration of the role of serial valgus casting, especially in the early stages of insult and limited to walking time, as a preventive measure against ischaemic chondronecrosis and its complications.

In conclusion, this hypothesis sheds light on a novel mechanism of Blount’s disease. Further research is warranted to validate and refine this proposition, offering promising avenues for addressing a century-long enigma in its aetiology.

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunity.

The preterm newborn is susceptible to many diseases related to oxidative stress, and supplemental oxygen therapy and its interaction with inflammatory processes may be a contributing factor to their underlying pathophysiology. Supplemental oxygen therapy can lead to over-oxygenation, and can complicate ischemia–reperfusion processes, which in turn can promote oxidative stress pathways. We hypothesize that the optimal dose of supplemental oxygen therapy likely varies for each preterm infant based on their unique and developing physiology, and may be adjusted through the assessment autonomic nervous function and pulmonary resilience by measuring heart rate variability. We present preliminary findings demonstrating that among extremely preterm infants with low-to-moderate heart rate characteristics index (HRCi) scores (indicating healthy ANS function) during the first six postnatal days, exposure to a low target oxygen saturation range was associated with decreased risk of the composite outcome of death by 36 weeks postmenstrual age (PMA), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and/or retinopathy of prematurity (ROP). This suggests a novel therapeutic approach to supplemental oxygen delivery in the neonatal intensive care unit (NICU) wherein the HRCi can be leveraged to guide the prescription of individualized target oxygen saturation ranges that are responsive to each infant’s unique and dynamic physiology, minimizing the risks of morbidity and mortality.